Mutant mice serve as a source of cultured primary cell strains and immortalized cell lines that are specifically deficient in TSG function. The changing phenotype of these cells in culture are being used to probe the normal functions of TSGs and to characterize the effects of loss of function. Such cells can be also utilized in transduction experiments that may involve the homologous TSGs as well other TSGs, or in cell fusion representing different complementations. Significantly, such cells will be used to establish surrogate end-points to evaluate the effects of chemopreventive agents. APC mutant mice represent one of the most accurate experimental models, as they principally develop colonic/intestinal adenomas histologically related to the tumors that defines familial adenomatous polyposis (FAP) in humans. Cells derived from APC mutant mice are being used for the in vitro screening of chemopreventive agents and the development of surrogate biomarkers during colorectal cancer development. The purpose of this project is to screen selected chemopreventive agents using mechanism-based surrogate biomarkers in transgenics-derived fibroblasts and epithelioid cells as follows: (1) spontaneous immortalization (2) genomic stability, (3) cell cycle control and molecular genetic changes that accompany immortalization (4) stabilization of telomeric DNA via activation of telomerase or by alternative mechanisms (5) prostaglandins production (6) anchorage independent growth.